Acid in the airways. Focus on "Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis".
Acid in the airways. Focus on "Hyperacidity of secreted fluid from submucosal glands in early cystic fibrosis".
复制标题
呼吸道中有酸。
DOI：
10.1152/ajpcell.00525.2005
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Wine,JeffreyJ
中科院分区：
文献类型：
--
作者：
Wine,JeffreyJ
囊性纤维化（CF）是由称为CF跨膜传导调节因子（CFTR）的阴离子通道缺陷引起的，该通道主要存在于上皮细胞的顶膜中。大多数CF症状，如汗液中的高盐和胰管、肠或输精管阻塞，都是由于电解质转运缺陷而发生的。在大多数器官中，病理生理学与CFTR介导的阴离子电导丧失之间的联系相对容易解释为CFTR介导的液体分泌丧失后的阻塞。这不是气道的情况，气道的主要症状是慢性气道感染。这些感染会引起大量的嗜酸性炎症，无情地破坏肺部。由于慢性肺部感染是CF患者死亡的主要原因，因此必须准确了解CFTR的丧失如何损害气道的先天防御。越来越多的共识认为，气道粘液缺陷的旧观点是正确的（8），但至关重要的是，由于许多研究人员在20世纪80年代早期的工作，该假设已经从寻找有缺陷的粘蛋白分子转移到气道表面上皮细胞和腺体改变液体和电解质转运的影响（26）。电解质运输被认为是气道先天防御系统所必需的，其至少有两个组成部分。通过粘膜纤毛和咳嗽清除将病原体从气道中物理清除的缺陷起着很大的作用（15）。此外，CF气道疾病的早期发作和严重性，与减少气道清除的其他疾病的较温和过程相反，表明气道中CFTR功能的丧失也损害了气道中发现的大量先天防御分子的有效性，从粘蛋白到许多抗菌剂、抗蛋白酶和抗炎化合物（9，23，26）.大多数先天防御分子由粘膜下腺体分泌。腺体对气道健康很重要，CFTR对适当的粘膜下腺体功能很重要（1-3，5，7，10，13，14，24-27）。例如，有和没有腺体的气管异种移植物的比较显示，含腺体的移植物中溶菌酶水平高得多，对感染的抵抗力更强（5，25），而对个体人气道腺体分泌物的测量显示，与正常腺体形成鲜明对比的是，CF腺体不分泌VIP或毛喉素（14）。与这种绝对缺陷相反，CF腺体中的乙酰胆碱腺体分泌持续存在，但数量似乎减少，粘度增加，但离子或pH值没有其他变化（22）。这些发现，以及其他研究表明，无论是毛喉素还是卡巴胆碱刺激的腺体粘液的pH值相等，都与基于Calu-3细胞的腺体功能模型不一致。
CYSTIC FIBROSIS (CF) is caused by defects in an anion channel called CF transmembrane conductance regulator (CFTR) that is found primarily in the apical membranes of epithelial cells. Most CF symptoms, such as high salt in sweat and obstruction of the pancreatic ducts, intestine, or vas deferens occur because of defective electrolyte transport. In most organs, the link between pathophysiology and loss of CFTR-mediated anion conductance is relatively easy to explain as obstruction following the loss of CFTR-mediated fluid secretion. This is not the situation in the airways, where the major symptom is chronic airway infection. These infections provoke massive neutrophilic inflammation that relentlessly destroys the lungs. Because chronic lung infection is by far the major cause of death in CF patients, it is essential to understand precisely how the loss of CFTR compromises the innate defenses of the airways. A growing consensus holds that the old idea of defective airway mucus (8) is correct, but crucially, because of work by many researchers in the early 1980s, the hypothesis has shifted away from searching for defective mucin molecules and is focused instead on the effects of altered fluid and electrolyte transport by airway surface epithelia and glands (26). Electrolyte transport is seen as essential to the innate defense system of the airways, which has at least two components. Defects in the physical removal of pathogens from the airways by mucociliary and cough clearance play a large role (15). In addition, the early onset and severity of CF airway disease, in contrast with the milder courses of other diseases that reduce airway clearance, suggest that the loss of CFTR function in the airways also compromises the effectiveness of the vast array of innate defense molecules found in the airways, from mucins to a host of antimicrobials, anti-proteases, and anti-inflammatory compounds (9, 23, 26).Most innate defense molecules are secreted by submucosal glands. Glands are important for airway health, and CFTR is important for proper submucosal gland function (1–3, 5, 7, 10, 13, 14, 24–27). For example, comparison of tracheal xenografts with and without glands revealed much higher levels of lysozyme and greater resistance to infection in the glandcontaining grafts (5, 25), whereas measures of secretion from individual human airway glands showed that, in marked contrast to normal glands, CF glands do not secrete to VIP or forskolin (14). In contrast with this absolute defect, gland secretion to acetylcholine persists in CF glands, but appeared to be diminished in quantity and to have increased viscosity, but no other changes in ions or pH (22). These findings, and other work indicating equivalent pH of gland mucus stimulated either by forskolin or carbachol, are at odds with a model of gland function based on the Calu-3 cell
登录
查看更多内容
环 GMP 水平增加会刺激韧带成纤维细胞产生弹性蛋白，而环 AMP 则可逆转这种情况。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Mecham,RP;Levy,BD;Morris,SL;Madaras,JG;Wrenn,DS
通讯作者：
Wrenn,DS
胰岛素样生长因子 I（生长调节素 C）诱导主动脉组织中弹性蛋白原的合成。
DOI：
10.1016/s0174-173x(87)80007-9
发表时间：
1987
期刊：
Collagen and related research
影响因子：
--
作者：
Foster,J;Rich,CB;Florini,JR
通讯作者：
Florini,JR
DOI：
10.1083/jcb.90.2.332
发表时间：
1981-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mecham RP;Lange G;Madaras J;Starcher B
通讯作者：
Starcher B
糖皮质激素刺激分化的牛韧带成纤维细胞中弹性蛋白的产生，但不诱导未分化细胞中弹性蛋白的合成。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Mecham,RP;Morris,SL;Levy,BD;Wrenn,DS
通讯作者：
Wrenn,DS
重组转化生长因子-β对猪主动脉平滑肌细胞的弹性作用。
DOI：
10.1016/0006-291x(88)90224-0
发表时间：
1988
影响因子：
3.1
作者：
Liu,JM;Davidson,JM
通讯作者：
Davidson,JM